Apparatus for biological sensing and alerting of pharmaco-genomic mutation

ABSTRACT

Electronic label processor compares bioinformatic values to determine pharmaco-genomic mutation associated with host. Label display indicates pharmaco-genomic mutation, which is network-accessible for modified medical message. Bioinformatic values are determined preferably at different times.

CROSS-REFERENCE TO RELATED APPLICATION

This application is a continuation of the U.S. patent application Ser.No. 10/277,213 filed on Oct. 18, 2002 now abandoned.

FIELD OF INVENTION

Field covers electronic labeling apparati and methods, particularly forpharmaco-genomic mutation.

BACKGROUND

In various healthcare applications, labels are used to identifypatients, medicines, and other medical items and information.Traditionally, however, medical labels are generally static, i.e., fixedin informational content, and often constructed of paper or similarmaterial, which are then attached mechanically to adhere to certainobject patient or medicine. Because traditional labeling systems areinefficient, and sometimes prone to staff error, there is need forimproved approach. Moreover, in view of emerging technical andinformational complexities arising from genomic-based practice, there isfurther need for improved labeling scheme.

SUMMARY

Electronic label processor, which compares bioinformatic values todetermine pharmaco-genomic mutation, displays the mutation. Labels arenetwork-accessible for modified medical messages. Bioinformatic valuesare determined preferably at different times.

BRIEF DESCRIPTION OF FIGURES

The accompanying drawings, which are incorporated in and form a part ofthis specification, illustrate embodiments of the invention and togetherwith the description, serve to explain the principles of the invention:

FIG. 1A flow chart shows representative steps for pharmaco-genomicmutation labeling method.

FIG. 1B shows generalized diagram of pharmaco-genomic mutation labelapparatus.

FIG. 1C shows sample pharmaco-genomic mutation labeling system andnetwork.

DETAILED DESCRIPTION

As understood and defined herein, term “pharmaco-genomic mutation” isunderstood generally and broadly to mean an alteration, variation,polymorphism, or other detectable or measurable change from anaturally-occurring, normal, engineered, induced or previously-mutatedcondition in single or multiple target or candidate nucleic acid,oligonucleotide or regulatory sequence, gene of interest or underinvestigation, protein sequence or folding structure, enzyme or otherbio-molecular material obtained from a host cell or tissue sample, orany segment or region of DNA which may be transcribed into RNA, containan open reading frame, encode a protein, and include one or more DNAregulatory element to control expression of a transcribed region. Suchmutation is not necessarily indicative of pharmaceutical function oreffect, but may be indicative of genomic, kinetic, proteomic, ormetabolomic instability or loss of heterozygosity, for example; andrefer to any mutation associated with disease, such as cancer or otherpathological mono- or polygenic condition, disorder or syndrome. Suchmutation term may comprise any single or multiple nucleotide insertion,deletion, rearrangement, transition, translation, tranversion,substitution, frame-shifting, repeat, or chromosomal rearrangement.

Moreover, term “bioinformatic value” is understood generally and broadlyto mean one or more digital or analog data-structure, text, object,signal, marker, code, tag, map, or other electronically-representableinformation, meta-information, or annotation that refers, corresponds,indicates, suggests, or is otherwise associated with a pharmaco-genomicmutation, or associated expression or pathway thereof, that is detected,measured, or otherwise determined to apply or be associatedphenotypically with a given host, or host group, or biological materialobtained or derived therefrom. Such value may be electronically stored,accessed, indexed, displayed, visualized, transmitted, modified,updated, compressed, secured, mined, searched, modeled, screened,profiled, or otherwise computationally processed.

For example, in accordance with mutation labeling or epidemiologicalaspect of present invention, one or more bioinformatic value may bedetermined from sensor or other host information to indicate presence orsuggest risk of pharmaco-genomic mutation, such as disease or disorderrelated to hemoglobin, trinucleotide repeat expansion, micro-deletionsyndrome, leukemia or solid tumor, metabolism (e.g., carbohydrate, aminoacid, lipid, organic acid, urea cycle, energy production, or heavy metaltransport disorder or defect), mucopolysaccharidoses, lysosomal storage,major histocompatibility complex, birth defect or syndrome, cancer,coronary heart disease.

Such pharmaco-genomic mutation may be determined or suggested by varioussensor or related processing (e.g., Southern blotting, direct DNAsequencing, SSCP analysis, DGGE analysis, DNA mismatch cleavage, ASOhybridization, mass spectrometry, DNA chip hybridization, proteintruncation, or other detection or sensing approach) described herein fordetermining bioinformatic value.

Generally, labeling system and process are embodied using one or moredevices associated with one or more hosts. In accordance with one aspectof the present invention, such devices indicate when some genetic orother biological change is determined. For example, such change may be agenetic sequence mutation that is detected when comparing a priorsequence with another sequence. Each device may generate someindication, such as a visible or audible alert that reports such change.

Mutation labels alert medical professionals in prioritized orhierarchical manner, such that higher-risk likelihood or more serioustoxicity or patient risk are revealed graphically or audibly through I/O48 in emphasized or highlighted context. Such alert may further indicateor warn when wrong or inappropriate medication was or is delivered toparticular patient having pharmaco-genomic profile.

FIG. 1A flow chart shows representative steps for pharmaco-genomicmutation labeling method. Electronic label processor or deviceelectronically compares 20 bioinformatic values or data to one or moretested bioinformatic value or data 10 to determine pharmaco-genomicmutation and analysis 30, or clinical optimization associated with host.FIG. 1B shows generalized diagram of pharmaco-genomic mutation labelapparatus 40. Label input/output display 48 indicates pharmaco-genomicmutation, which may be network-accessible through wired, wireless orradio-frequency (RF) network communication interface 46 for modifiedmedical message. Bioinformatic values are stored remotely or locally inmemory 44 and determined or otherwise processed by controller ormicroprocessor 42 preferably at different times using sensor 49.

Optionally, label apparatus 40 is embodied in one or more mainframecomputer, engineering workstation, personal computer, network processor,patient-attached, local, adjacent or hand-held or mobile personaldigital assistant device, embedded controller, or other digital signalprocessing machine capable of electronic storage, display, and access tonetwork or sensor elements. FIG. 1C shows sample pharmaco-genomicmutation labeling system and network 50 with multiple nodes 60 coupledthereto, as well as label apparatus 40, which is associated withbiological or tissue host 70.

Optionally, label apparatus 40 couples to or includes one or more sensor49 for detecting, testing, screening, or generating a pharmaco-genomicmutation, bioinformatic value, or lack thereof, associated with aparticular host, or biomaterial therefrom in vitro or in vivo.Preferably, in vivo implantable sensor or label packaging is constructedto be nonthrombogenic and nontoxic.

For example, sensor 49 may comprise one or more integrated nucleic aciddiagnostic device, assay, or array of nucleic acid probes on biologicalchips or plates, available commercially from Affymetrix, Inc. (SantaClara, Calif.), capable of sample acquisition and analysis for nucleicacid-based diagnostic, de novo sequencing, or detecting reaction betweentarget molecules and probes.

Sensor 49 may also comprise one or more miniature, implantableidentification device or “VeriChip”, available commercially from AppliedDigital Solutions, Inc. (Palm Beach, Fla.), capable of generating hostor patient or medical information and other bioinformatic values.

It is further contemplated herein that sensor 49 may also employ one ormore system or method for detecting or generating pharmaco-genomicmutation or bioinformatic value using integrated chip refractive-indexmicro-interferometry detection, using coherent VCSEL, laser diode, orHe—Ne laser source, etched substrate capillary channel for samplereception and analysis, and reflected laser-light reflectionphotodetector; or affinity-based biosensor based on optical evanescentwave detector using flow-based surface plasmon resonance inmicro-fabricated integrated fluidic cartridge to capture taggedproteins, thiol coupling, or coil-coil interaction, wherein resonanceangle is continuously monitored to detect changes in refractiveresonance angle and refractive index corresponding to changes in masswhen certain ligand binds to, or dissociates from, immobilized bindingpartner.

Also sensor 49 may detect or generate pharmacogenomic mutation orbioinformatic value using semiconductor nanocrystal or so-calledquantum-dot device as detectable label or probe by linking or bonding toone or more affinity molecules of a detectable substance in an analyte,whereupon such nanocrystal probe in response to a first energyassociated with a presence of detectable substance within materialbonded to the probe, excites the nanocrystal in the probe and causes theprobe to provide a second energy or generate or fluoresce a distinctwavelength signal indicating the presence.

It is further contemplated herein that sensor 49 may employ one or moresystem or method for detecting or generating pharmaco-genomic mutationor bioinformatic value using mass spectrometry, or native enzyme orantibody reactions for protein sequencing or detection; orchromatographic on-chip separation with mass spectrometry using surfaceenhanced laser desorption and ionization time of flight massspectrometry, available commercially from Ciphergen Biosystems (PaloAlto, Calif.), using chip array to detect protein biomarkers indicativeof disease.

Also sensor 49 may detect or generate pharmacogenomic mutation orbioinformatic value using one or more micro-electrical-mechanical ormolecular systems, devices, probes, or arrays, or assays structurallycomprising dendrimer, buckyball, fullerene, wire, or nanotube, forexample, to monitor, detect, control, or otherwise process electrically,mechanically, optically, or chemically biological or genetic molecules,or contaminant agents or indicators thereof, such as anthrax, smallpox,botulism, tularemia, viral hemorrhagic fever, or plague.

Optionally, pharmaco-genomic mutation or bioinformatic value isindicated, determined, or generated, in part, by detecting alteration intarget nucleic acid, described by Shuber in U.S. Pat. No. 6,428,964; byidentifying mutation in gene of interest without phenotypic guide,described by Goodfellow in U.S. Pat. No. 5,994,075; by identifying genesunderlying defined phenotypes, described by Iris et al in U.S. Pat. No.6,221,585; by using computer program and database structure fordetecting molecular binding events, described by Hefti in U.S. Pat. No.6,395,480; by using computer-assisted method and apparatus foridentification and characterization of biomolecules in biologicalsample, described by Parekh et al. in U.S. Pat. No. 6,064,754; or usingmethods, software, and apparatus for identifying genomic regionsharboring gene associated with detectable trait, described by Schork etal. in U.S. Pat. No. 6,291,182; which references are hereby incorporatedby reference as appropriate.

Furthermore, it is contemplated herein that pharmaco-genomic mutation orbioinformatic value may be indicated, determined, or generated usingvarious mutation detection techniques, and applicable sensor andprocesses therefore, such as:

-   -   Southern blotting (to detect insertions, deletions, and        rearrangements, as well as ordering of DNA fragments into        physical map), using DNA digestion with restriction enzyme,        resolution of fragments with agarose gel electrophoresis,        transfer of DNA to nylon membrane and hybridization of labeled        probe to DNA fragments;    -   Direct DNA sequencing (to detect insertions, deletions, point        mutations, and rearrangements), using determination of linear        order of nucleotides of test DNA, specific nucleotide detected        by chemical cleavage, dideoxychain termination, or fluorochorome        dye;    -   Single-strand conformational polymorphism (SSCP) analysis (to        detect small insertions or deletions, and point mutations),        using differential electrophoretic mobility of single-stranded        test DNA with different secondary structures or conformations        through non-denaturing gel;    -   Denaturing gradient gel electrophoresis (DGGE) analysis (to        detect small insertions or deletions, and point mutations),        using migration of DNA duplexes through electrophoretic gel with        increasing amounts of denaturant (e.g., chemical, temperature)        until DNA strands separate; resolution of alleles by        Polyacrylamide gel electrophoresis (PAGE);    -   DNA mismatch cleavage (to detect small insertions or deletions,        and point mutations), using hybridization of labeled proe to        test DNA, cleavage of DNA at site of base-pairing mismatch;    -   Allele-specific oligonucleotide (ASO) hybridization (to detect        allele(s) of known composition), using preferential        hybridization of labeled probe to test DNA with uniquely        complementary base composition;    -   Mass spectrometry (to detect small insertions or deletions, and        point mutations), using detection of physical mass of sense and        anti-sense strands of test DNA;    -   DNA chip hybridization (to detect test DNA of known        composition), using hybridization of test DNA to arrays of        oligonucloeotides ordered on silicon chip; or    -   Protein truncation (to detect frameshift, splice site, or        nonsense mutations that truncate protein product), using test        RNA to make cDNA by reverse transcriptase-Polymerase Chain        Reaction (TR-PCR) with 5′ primer containing T7 promoter, cDNA        translated and product resolved by sodium dodecyl sulfate        (SDS)-PAGE.

Optionally, pharmaco-genomic mutation or bioinformatic value isindicated, determined, or generated, in part, to describe or suggest oneor more hemoglobin disease, disorder, or risk, such as:

-   -   sickle cell disease, associated with or corresponding to        β-globin missense mutation;    -   Hb H disease, associated with or corresponding to deletion or        abnormality of three of four α-globin genes;    -   Hydrops fetalis (Hb Barts), associated with or corresponding to        deletion or abnormality of all four α-globin genes;    -   β°-Thalassemia, associated with or corresponding to nonsense,        frameshift, or slice site donor or acceptor mutations, and no        β-globin production; or    -   β⁺-Thalassemia, associated with or corresponding to missense,        regulatory, or splice site consensus sequence or cryptic splice        site mutation(s), and small of amount of β-globin production.

Optionally, pharmaco-genomic mutation or bioinformatic value isindicated, determined, or generated, in part, to describe or suggest oneor more disease, disorder, or risk associated with trinucleotide repeatexpansions, such as:

Category 1:

-   -   Huntington disease, associated with or corresponding to        exon-located CAG repeat sequence of 36 to 100 or more (normal: 6        to 34);    -   Spinal and bulbar muscular atrophy, associated with or        corresponding to exon-located CAG repeat sequence of 40 to 62        (normal: 11 to 34);    -   Spinocerebellar ataxia, type 1, associated with or corresponding        to exon-located CAG repeat sequence of 41 to 81 (normal: 6 to        39);    -   Spinocerebellar ataxia, type 2, associated with or corresponding        to exon-located CAG repeat sequence of 35 to 59 (normal: 15 to        29);    -   Spinocerebellar ataxia, type 3 (Machado-Joseph disease),        associated with or corresponding to exon-located CAG repeat        sequence of 68 to 79 (normal: 13 to 36);    -   Spinocerebellar ataxia, type 6, associated with or corresponding        to exon-located CAG repeat sequence of 21 to 27 (normal: 4 to        16);    -   Spinocerebellar ataxia, type 7, associated with or corresponding        to exon-located CAG repeat sequence of 38 to 200 (normal: 7 to        35);    -   Dentatorubral-pallidolusian atrophy/Haw River syndrome,        associated with or corresponding to exon-located CAG repeat        sequence of 49 to 88 (normal: 7 to 25);    -   Pseudoachondroplasia/multiple epiphyseal dysplasia, associated        with or corresponding to exon-located GAC repeat sequence of 6        to 7 (normal: 5);    -   Oculopharyngeal muscular dystrophy, associated with or        corresponding to exon-located GCG repeat sequence of 7 to 13        (normal: 6);    -   Cleidocranial dysplasia, associated with or corresponding to        exon-located GCG GCT GCA repeat sequence of 27 (normal: 17);    -   Synpolydactyly, associated with or corresponding to exon-located        GCG GCT GCA repeat sequence of 22 to 25 (normal 15);        Category 2:    -   Myotonic dystrophy, associated with or corresponding to CTG        repeat sequence of 100 to several thousand (normal 5 to 37) in        3′ untranslated region;    -   Friedreich's ataxia, associated with or corresponding to        intron-located GAA repeat sequence of 200 to 900 or more        (normal: 7 to 22);    -   Fragile X syndrome (FRAXA), associated with or corresponding to        CGG repeat sequence of 200 to 2,000 or more (normal: 6 to 52) in        5′ untranslated region;    -   Fragile site FRAXE, associated with or corresponding to GCC        repeat sequence of 200 or more (normal: 6 to 35) in 5′        untranslated region;    -   Spinocerebellar ataxia, type 8, associated with or corresponding        to CTG repeat sequence of 107 to 127 (normal: 16 to 37) in 3′        untranslated region;    -   Spinocerebellar ataxia, type 12, associated with or        corresponding to CAG repeat sequence of 66 to 78 (normal: 7        to 28) in 5′ untranslated region; or    -   Progressive myoclonic epilepsy, type 1, associated with or        corresponding to 12-bp repeat motif of 30 to 75 (normal: 2 to 3)        in 5′ untranslated region.

Optionally, pharmaco-genomic mutation or bioinformatic value isindicated, determined, or generated, in part, to describe or suggest oneor more disease, disorder, or risk associated with micro-deletionsyndromes, such as:

-   -   Prader-Willi syndrome, associated with or corresponding to        chromosomal deletion 15q11-13;    -   Langer-Giedeion syndrome, associated with or corresponding to        chromosomal deletion 8q24;    -   Miller-Dieker syndrome, associated with or corresponding to        chromosomal deletion 17p13.3;    -   DiGeorge anomaly/velo-cardio-facial syndrome, associated with or        corresponding to chromosomal deletion 22q11;    -   Williams syndrome, associated with or corresponding to        chromosomal deletion 7q1; or    -   Aniridia/Wilms tumor syndrome, associated with or corresponding        to chromosomal deletion 11p13.

Optionally, pharmaco-genomic mutation or bioinformatic value isindicated, determined, or generated, in part, to describe or suggest oneor more disease, disorder, or risk associated with leukemias and solidtumors, such as:

Leukemias:

-   -   Chronic myelogenous leukemia, associated with or corresponding        to chromosomal aberration t(9;22)(q34;q11);    -   Acute myeloblastic leukemia, associated with or corresponding to        chromosomal aberration t(8;21)(q22;q22);    -   Acute promeolocytic leukemia, associated with or corresponding        to chromosomal aberration t(15;17)(q22;q11-22);    -   Acute non-lymphocytic leukemia, associated with or corresponding        to chromosomal aberration+8,−7,−5,del(5q),del(20q);        Solid Tumors:    -   Burkitt lymphoma, associated with or corresponding to        chromosomal aberration t(8;14)(q24;q32);    -   Ewing sarcoma, associated with or corresponding to chromosomal        aberration t(11;22)(q24;q12);    -   Meningioma, associated with or corresponding to chromosomal        aberration Monosomy 22;    -   Retinoblastoma, associated with or corresponding to chromosomal        aberration del(13)(q14); or    -   Wilms tumor, associated with or corresponding to chromosomal        aberration del(11)(p13).

Optionally, pharmaco-genomic mutation or bioinformatic value isindicated, determined, or generated, in part, to describe or suggest oneor more disease, disorder, or risk associated with metabolism, such as:

Carbohydrate Disorders:

-   -   Classical glactosemia, associated with or corresponding to        mutant gene product galactose-1-phosphate uridyl transferace at        chromosomal location 9p13;    -   Hereditary fructose intolerance, associated with or        corresponding to mutant gene product fructose 1,6-biphospate        aldolase at chromosomal location 9q13-q32;    -   Fructosuria, associated with or corresponding to mutant gene        product fructokinase at chromosomal location 2p23;    -   Hypolactasia (adult), associated with or corresponding to mutant        gene product lactase at chromosomal location 2q21;    -   Diabetes mellitus (type I), associated with or corresponding to        mutant polygenic products;    -   Diabetes mellitus (type H), associated with or corresponding to        mutant polygenic products;    -   Maturity onset diabetes of youth (MODY), associated with or        corresponding to mutant gene product glucokinase (60%) at        chromosomal location 7p13;        Amino Acid Disorders:    -   Phenylketonuria, associated with or corresponding to mutant gene        product phenylalanine hydroxylase at chromosomal location 12q24;    -   Tyrosinemia, type 1, associated with or corresponding to mutant        gene product fumarylacetoacetate hydrolase at chromosomal        location15q23-25;    -   Maple syrup urine disease, associated with or corresponding to        mutant gene product branched-chain α-ketoacid decarboxylase        (subunits at multiple loci);    -   Alkaptonuria, associated with or corresponding to mutant gene        product homogentisic acid oxidase at chromosomal location 3q2;    -   Homocystinuria, associated with or corresponding to mutant gene        product cystathionine β-synthase at chromosomal location 21q2;    -   Oculocutaneous albinism, associated with or corresponding to        mutant gene product tyrosinase at chromosomal location 11q;    -   Cystinosis, associated with or corresponding to mutant gene        product CTNS at chromosomal location 17p13;    -   Cystinuria, associated with or corresponding to mutant gene        product SLC3A1 (type I) at chromosomal location 2p, or mutant        gene product SLC7A9 (types II & III) at chromosomal location        19q13;        Lipid Disorders:    -   MCAD, associated with or corresponding to mutant gene product        medium-chain acyl-Coa dehydrogenase at chromosomal location        1p31;    -   LCAD, associated with or corresponding to mutant gene product        long-chain acyl-CoA dehydrogenase at chromosomal location        2q34-q35;    -   SCAD, associated with or corresponding to mutant gene product        short-chain acyl-Coa dehydrogenase at chromosomal location        12q22qter;        Organic Acid Disorders:    -   Methylmalonic acidemia, associated with or corresponding to        mutant gene product methylmalonyl-CoA at chromosomal location        6p;    -   Propionic acidemia, associated with or corresponding to mutant        gene product propionyl-CoA carboxylase at chromosomal location        13q32, 3q;        Urea Cycle Defects:    -   Ornithine transcarbamylase deficiency, associated with or        corresponding to mutant gene product ornithine carbamyl        transferase at chromosomal location Xp21;    -   Carbamyl phosphate synthetase deficiency, associated with or        corresponding to mutant gene product caramyl phosphate        synthetase I at chromosomal location 2p; Argininosuccinic acid        synthetase deficiency, associated with or corresponding to        mutant gene product argininosuccinic acid synthetase at        chromosomal location 9q34;        Energy Production Defects:    -   Cytochrome C oxidase deficiency, associated with or        corresponding to mutant gene product cytochrome oxidase peptides        at multiple loci;    -   Pyruvate carboxylase deficiency, associated with or        corresponding to mutant gene product pyruvate carboxylase at        chromosomal location 11q;    -   Pyruvate dehydrogenase complex (E₁) deficiency, associated with        or corresponding to mutant gene product pyruvate decarboxylase,        E₁α at chromosomal location Xp22;    -   NADH-CoQ reductase deficiency, associated with or corresponding        to multiple nuclear genes at multiple loci;        Heavy Metal Transport Defects:    -   Wilson disease, associated with or corresponding to mutant gene        product ATP7B at chromosomal location 13q14;    -   Menkes disease, associated with or corresponding to mutant gene        product ATP7A at chromosomal location Xq13; or    -   Hemochromatosis, associated with or corresponding to mutant gene        product HFE at chromosomal location 6p21.

Optionally, pharmaco-genomic mutation or bioinformatic value isindicated, determined, or generated, in part, to describe or suggest oneor more disease, disorder, or risk associated withmucopolysaccharidoses, such as:

-   -   Hurler/Scheie, associated with or corresponding to mutant enzyme        α-L-Iduronidase;    -   Hunter, associated with or corresponding to mutant enzyme        Iduronate sulfatase;    -   Sanfilippo A, associated with or corresponding to mutant enzyme        Heparan-N-sulfamidase;    -   Sanfilippo B, associated with or corresponding to mutant enzyme        α-N-Acetylglucosaminidase;    -   Sanfilippo C, associated with or corresponding to mutant enzyme        Acetyl-CoA: α-glucosaminide N-acetyltransferase;    -   Sanfilippo D, associated with or corresponding to mutant enzyme        N-Acetylglucosamine-6-sulfatase;    -   Morquio A, associated with or corresponding to mutant enzyme        N-Acetylglucosamine-6-sulfatase;    -   Morquio B, associated with or corresponding to mutant enzyme        β-Galactosidase; Maroteaux-Lamy, associated with or        corresponding to mutant enzyme Aryl sulfatase B; or    -   Sly, associated with or corresponding to mutant enzyme        β-Glucuronidase.

Optionally, pharmaco-genomic mutation or bioinformatic value isindicated, determined, or generated, in part, to describe or suggest oneor more disease, disorder, or risk associated with lysosomal storage,such as:

-   -   Tay-Sachs, associated with or corresponding to mutant enzyme        β-Hexosaminidase (A isoenzyme);    -   Gaucher (type I; non-neuropathic), associated with or        corresponding to mutant enzyme β-Glucosidase;    -   Niemann-Pick, type 1A, associated with or corresponding to        mutant enzyme Sphingomyelinase;    -   Fabry, associated with or corresponding to mutant enzyme        α-Galactosidase;    -   GM1 gangliosidosis (infantile), associated with or corresponding        to mutant enzyme β-Galactosidase;    -   Krabbe, associated with or corresponding to mutant enzyme        β-Galactosidase (galactosylceramide-specific);    -   Metachromatic leukodystrophy (late-infantile), associated with        or corresponding to mutant enzyme Aryl sulfatase A;    -   Sandhoff, associated with or corresponding to mutant enzyme        β-Hexosaminidase (total);    -   Schindler, associated with or corresponding to mutant enzyme        α-N-Acetylgalactosaminidase; or    -   Multiple sulfatase deficiency, associated with or corresponding        to mutant enzyme Aryl sulfatases A B C.

Optionally, pharmaco-genomic mutation or bioinformatic value isindicated, determined, or generated, in part, to describe or suggest oneor more genetic disease, disorder, or risk such as:

-   -   α-1-Antitrypsin deficiency, associated with or corresponding to        disease gene product serine protease inhibitor at chromosome        location 14q;    -   α-Thalassemia, associated with or corresponding to disease gene        product α-Globin component of hemoglobin at chromosome location        16p;    -   β-Thalassemia, associated with or corresponding to disease gene        product β-Globin component of hemoglobin at chromosome location        11p;    -   Achondroplasia, associated with or corresponding to disease gene        product fibroblast growth factor receptor 3 at chromosome        location 4p;    -   Adult polycystic kidney disease, associated with or        corresponding to disease gene products polycystin-1 membrane        protein at chromosome location 16p, polycystin-2 membrane        protein at chromosome location 4p;    -   Albinism, oculocutaneous (type 1), associated with or        corresponding to disease gene product tyrosinase at chromosome        location 11q;    -   Albinism, oculocutaneous (type 2), associated with or        corresponding to disease gene product tyrosine transporter at        chromosome location 15q;    -   Alzheimer disease, associated with or corresponding to disease        gene products presenilin 1 at chromosome location 14q,        presenilin 2 at chromosome location 1q, apolipoprotein E at        chromosome location 19q, β-Amyloid precursor protein at        chromosome location 21q;    -   Amyotrophic lateral sclerosis, associated with or corresponding        to disease gene product superoxide dismutase 1 at chromosome        location 21q;    -   Angelman syndrome, associated with or corresponding to disease        gene product ubiquitin-protein ligase E3A at chromosome location        15q;    -   Ataxia telangiectasia, associated with or corresponding to        disease gene product cell cycle control protein at chromosome        location 11q;    -   Beckwith-Wiedemann syndrome, associated with or corresponding to        disease gene product insulin-like growth factor II at chromosome        location 11p;    -   Bloom syndrome, associated with or corresponding to disease gene        product RecQ helicase at chromosome location 15q;    -   Breast cancer (familial), associated with or corresponding to        disease gene products BRCA1 tumor suppressor at chromosome        location 17q, BRCA2 tumor suppressor at chromosome location 13q;    -   Charcot-Marie-Tooth disease (type 1B), associated with or        corresponding to disease gene product myelin protein zero at        chromosome location 1q; (type 1A), associated with or        corresponding to disease gene product peripheral myelin protein        22 at chromosome location 17p; (CMTX1), associated with or        corresponding to disease gene product connexin-32 gap junction        protein at chromosome location Xq;    -   Cystic fibrosis, associated with or corresponding to disease        gene product cystic fibrosis transmembrane regulator (CFTR) at        chromosome location 7q;    -   Deafness (nonsyndromic), associated with or corresponding to        disease gene products connexin-26 gap junction protein at        chromosome location 13q, actin polymerization regulator at        chromosome location 5q, KCNQ4 potassium channel at chromosome        location 1p.    -   Diabetes (MODY1), associated with or corresponding to disease        gene product hepatocyte nuclear factor-4α at chromosome location        20q; (MODY2), associated with or corresponding to disease gene        product glucokinase at chromosome location 7p; (MODY3),        associated with or corresponding to disease gene product        hepatocyte nuclear factor-1α at chromosome location 1q;    -   Duchenne/Becker muscular dystrophy, associated with or        corresponding to disease gene product dystrophin at chromosome        location Xp;    -   Ehlers-Danlos syndrome, associated with or corresponding to        disease gene product collagen (COL3A1) at chromosome location        2q;    -   Ellis van Creveld syndrome, associated with or corresponding to        disease gene product leucine zipper at chromosome location 4p;    -   Familial polyposis coli, associated with or corresponding to        disease gene product APC tumor suppressor at chromosome location        5q;

Fragile X syndrome, associated with or corresponding to disease geneproduct FMR1 RNA-binding protein at chromosome location Xq;

-   -   Friedreich ataxia, associated with or corresponding to disease        gene product Frataxin mitochondrial protein at chromosome        location 9q;    -   Galactosemia, associated with or corresponding to disease gene        product Galactose-1-phosphate-uridyltransferase at chromosome        location 9p;    -   Hemochromatosis, associated with or corresponding to disease        gene product transferring receptor binding protein at chromosome        location 6p;    -   Hemophilia A, associated with or corresponding to disease gene        product clotting factor VIII at chromosome location Xq;    -   Hemophelia B, associated with or corresponding to disease gene        product clotting factor IX at chromosome location Xq;    -   Hereditary nonpolyposis colorectal cancer, associated with or        corresponding to disease gene products MLH1 DNA mismatch repair        protein at chromosome location 3p, MLH2 DNA mismatch repair        protein at chromosome location 2p, PMS1 DNA mismatch repair        protein at chromosome location 2q, PMS2 DNA mismatch repair        protein at location 7p, MSH6 DNA mismatch repair protein at        chromosome location 2p;    -   Hirschsprung disease (type 1), associated with or corresponding        to disease gene product RET tyrosine kinase proto-oncogene at        chromosome location 10q; (type 2), associated with or        corresponding to disease gene product endothelin receptor type B        at chromosome location 13q;    -   Huntington disease, associated with or corresponding to disease        gene product huntingtin at chromosome location 4p;    -   Hypercholesterolemia (familial), associated with or        corresponding to disease gene product LDL receptor at chromosome        location 19p;    -   Long QT syndrome (LQT3), associated with or corresponding to        disease gene SCN5A cardiac sodium channel at chromosome location        3p; (LQT2), associated with or corresponding to disease gene        product HERG cardiac potassium channel at chromosome location        7q; (LQT1), associated with or corresponding to disease gene        product KVLQT1 cardiac potassium channel a submit at chromosome        location 11p; (LQTS), associated with or corresponding to        disease gene product KCNE1 cardiac potassium channel subunit at        chromosome location 21q; (LQT6), associated with or        corresponding to disease gene product KCNE2 cardiac potassium        channel at chromosome location 21q;    -   Marfan syndrome, associated with or corresponding to disease        gene product fibrillin-1 at chromosome location 15q;    -   Melanoma (familial), associated with or corresponding to disease        gene products cyclin-dependent kinase inhibitor tumor suppressor        at chromosome location 9p, cyclin-dependent kinase-4 at        chromosome location 12q;    -   Myotonic dystrophy, associated with or corresponding to disease        gene product protein kinase at chromosome location 19q;    -   Myoclonus epilepsy (Unverricht-Lundborg), associated with or        corresponding to disease gene product cystatin B cystein        protease inhibitor at chromosome location 21q;    -   Neurofibromatosis (type 1), associated with or corresponding to        disease gene product neurofibromin tumor suppressor at        chromosome location 17q; (type 2), associated with or        corresponding to disease gene product merlin (schwannomin) tumor        suppressor at chromosome location 22q;    -   Parkinson disease (familial), associated with or corresponding        to disease gene product α-synuclein at chromosome location 4q;    -   Phenylketonuria, associated with or corresponding to disease        gene product phenylalanine hydroxylase at chromosome location        12q;    -   Retinitis Pigmentosa, associated with or corresponding to        disease gene products rhodopsin at chromosome location 3q, TULP1        tubby-like protein at chromosome location 6p, Retina-specific        ABC transporter at chromosome location 1p, pheripherin at        chromosome location 6p, rod outer segment membrane protein at        chromosome location 11q, retinal rod photoreceptor cGMP        phosphodiesterase subunit at chromosome location 4p, retinal rod        photoreceptor cGMP phosphodiesterase a subunit at chromosome        location 5q, retinal rod cGMPgated channel a subunit at        chromosome location 4p, myosin VITA at chromosome location 11q;    -   Retinoblastoma, associated with or corresponding to disease gene        product pRb tumor suppressor at chromosome location 13q;    -   Rett syndrome, associated with or corresponding to disease gene        product methyl CpG binding protein at chromosome location Xq;    -   Sickle-cell disease, associated with or corresponding to disease        gene product β-globin component of hemoglobin at chromosome        location 11p;    -   Smith-Lemli-Opitz syndrome, associated with or corresponding to        disease gene product 7-dehydrocholesterol reductase at        chromosome location 11q;    -   Stargardt disease, associated with or corresponding to disease        gene product ATP-binding cassette transporter at chromosome        location 1p;    -   Tay-Sachs disease, associated with or corresponding to disease        gene product hexosaminidase A at chromosome location 15q;    -   Tuberous sclerosis (type 1), associated with or corresponding to        disease gene product hamartin tumor suppressor at chromosome        location 9q; (type 2), associated with or corresponding to        disease gene product tuberin tumor suppressor at chromosome        location 16p;    -   Usher syndrome, associated with or corresponding to disease gene        product myosin VITA at chromosome location 11q;    -   Waardenburg syndrome (types 1 and 3), associated with or        corresponding to disease gene product PAX3 transcription factor        at chromosome location 2q; (type 2), associated with or        corresponding to disease gene product MITF leucine zipper        protein at chromosome location 3p; (type 4), associated with or        corresponding to disease gene product endothelin 3 or endothelin        B receptor at chromosome location 14q;    -   Wilms tumor, associated with or corresponding to disease gene        product WT1 zind finger protein tumor suppressor at chromosome        location 11p;    -   Wilson disease, associated with or corresponding to disease gene        product copper transporting ATPase at chromosome location 13q;        or    -   von Willebrand disease, associated with or corresponding to        disease gene product von Willebrand clotting factor at        chromosome location 12q.

Optionally, pharmaco-genomic mutation or bioinformatic value isindicated, determined, or generated, in part, to describe or suggest oneor more major histocompatibility complex (MHC) disease, disorder, orrisk associated with MHC human leukocyte antigen (HLA)-associatedallele, such as:

-   -   Type 1 diabetes, associated with or corresponding to allele DR3        and DR4;    -   Ankylosing spondylitis, associated with or corresponding to        allele B27;    -   Narcolepsy, associated with or corresponding to allele DR2;    -   Celiac disease, associated with or corresponding to allele DR3,        DR7;    -   Rheumatoid arthritis, associated with or corresponding to allele        DR1, DR4;    -   Myasthenia gravis, associated with or corresponding to allele        DR3, DR7;    -   Multiple sclerosis, associated with or corresponding to allele        DR2;    -   Pemphigus vulgaris, associated with or corresponding to allele        DR4;    -   Systemic lupus erythematosus, associated with or corresponding        to allele DR2, DR3;    -   Hemochromatosis, associated with or corresponding to allele A3;    -   Malaria, associated with or corresponding to allele B53;    -   Graves disease, associated with or corresponding to allele DR3;    -   Psoriasis vulgaris, associated with or corresponding to allele        Cw6; or    -   Squamous cell cervical carcinoma, associated with or        corresponding to allele DQw3.

Optionally, pharmaco-genomic mutation or bioinformatic value isindicated, determined, or generated, in part, to describe or suggest oneor more birth defect, syndome, or risk associated with particular gene,such as:

-   -   Branchio-oto-renal syndrome, associated with or corresponding to        gene BOR1;    -   Stickler syndrome, associated with or corresponding to gene        COL2A1;    -   Schizencephaly syndrome, associated with or corresponding to        gene EMX2;    -   Ellis-van Creveld syndrome, associated with or corresponding to        gene EvC;    -   Creig syndrome, associated with or corresponding to gene GLI3;    -   Pallister-Hall syndrome, associated with or corresponding to        gene GLI3;    -   Polydactyly type A syndrome, associated with or corresponding to        gene GLI3;    -   Hand-foot-genital syndrome, associated with or corresponding to        gene HOXA13;    -   Synpolydactyly syndrome, associated with or corresponding to        gene HOXD13;    -   Piebaldism syndrome, associated with or corresponding to gene        KIT;    -   Nail-patella syndrome, associated with or corresponding to gene        LMX1;    -   Cleft lip/palate syndrome, associated with or corresponding to        gene MSX1;    -   Multiple synostosis syndrome, associated with or corresponding        to gene Noggin;    -   Ectrodactyly/ectodermal dysplasia syndrome, associated with or        corresponding to gene p63;    -   Kidney and optic nerve defect syndrome, associated with or        corresponding to gene PAX2;    -   Waardenburg syndrome, associated with or corresponding to gene        PAX3;    -   Aniridia syndrome, associated with or corresponding to gene        PAX6;    -   Oligodontia syndrome, associated with or corresponding to gene        PAX9;    -   Rieger syndrome, associated with or corresponding to gene RIEG1;    -   Townes-Brocks syndrome, associated with or corresponding to gene        SALL1;    -   Holoprosencephaly syndrome, associated with or corresponding to        gene SHH;    -   Campomelic syndrome, associated with or corresponding to gene        SOX9;    -   Hirschsprung syndrome, associated with or corresponding to gene        SOX10;    -   Ulnar-mammary syndrome, associated with or corresponding to gene        TBX3;    -   Holt-Oram syndrome, associated with or corresponding to gene        TBS;    -   Treacher Collins syndrome, associated with or corresponding to        gene TCOF1;    -   Denys-Drash syndrome, associated with or corresponding to gene        WT1; or    -   Smith-Lemli-Opitz syndrome, associated with or corresponding to        gene 7-DHCR.

Optionally, pharmaco-genomic mutation or bioinformatic value isindicated, determined, or generated, in part, to describe or suggest oneor more cancer disease, disorder, or risk associated with tumorsuppressor gene, such as:

-   -   Retinoblastoma, osteosarcoma, associated with or corresponding        to gene RB1 (related p107, p130) at chromosome location 13q14;    -   Familial adenomatous polyposis, associated with or corresponding        to gene APC at chromosome location 5q21;    -   Neurofibromatosis type 1, associated with or corresponding to        gene NF1 at chromosome location 17q11;    -   Neurofibromatosis type 2, associated with or corresponding to        gene NF2 at chromosome location 22q12;    -   Li-Fraumeni syndrome, associated with or corresponding to gene        p53 (related p63, p73) at chromosome location 17p13;    -   Von Hippel-Lindau disease (renal cancer), associated with or        corresponding to gene VIAL at chromosome location 3p25;    -   Wilms tumor, associated with or corresponding to gene WT1 at        chromosome location 11p13;    -   Familial melanoma, associated with or corresponding to gene p16        (related p15) at chromosome location 9p21;    -   Familial breast/ovarian cancer, associated with or corresponding        to gene BRCA1 at chromosome location 17q21;    -   Familial breast cancer, associated with or corresponding to gene        BRCA2 at chromosome location 13q12;    -   Cowden disease (breast and thyroid cancer), associated with or        corresponding to gene PTEN at chromosome location 10q23;    -   Ataxia telangiectasia, associated with or corresponding to gene        AT at chromosome location 11q22; or    -   Li-Fraumeni syndrome, associated with or corresponding to gene        CHK2 at chromosome location 22q12.

Optionally, pharmaco-genomic mutation or bioinformatic value isindicated, determined, or generated, in part, to describe or suggest oneor more cancer disease, disorder, or risk associated with oncogene, suchas:

Growth Factors:

-   -   Stomach carcinoma, associated with or corresponding to oncogene        HST at chromosome location 11q13;    -   Glioma (brain tumor), associated with or corresponding to        oncogene SIS at chromosome location 22q12;        Growth Factor Receptors:    -   Multiple endocrine neoplasia, associated with or corresponding        to oncogene RET at chromosome location 10q;    -   Glioboastoma (brain tumor), breast cancer, associated with or        corresponding to oncogene erb-B at chromosome location 10q;    -   Promyelocytic leukemia, associated with or corresponding to        oncogene erb-A at chromosome location 17q11;    -   Neuroblastoma, associated with or corresponding to oncogene NEU        at chromosome location 17q11;        Signal Transduction Proteins:    -   Carcinoma of colon, lung, pancreas, associated with or        corresponding to oncogene H-RAS at chromosome location 11p15;    -   Melanoma, thyroid carcinoma, AML, associated with or        corresponding to oncogene K-RAS at chromosome location 12p12;    -   Chronic myelogenous leukemia, acute lymphocytic leukemia,        associated with or corresponding to oncogene Abl at chromosome        location 9q34;        Transcription Factors:    -   Neuroblastoma, lung carcinoma, associated with or corresponding        to oncogene N-myc at chromosome location 2p24;    -   Malignant melanoma, lymphoma, leukemia, associated with or        corresponding to oncogene MYB at chromosome location 6q22; or    -   Osteosarcoma, associated with or corresponding to oncogene Fos        at chromosome location 14q24.

Optionally, pharmaco-genomic mutation or bioinformatic value isindicated, determined, or generated, in part, to describe or suggest oneor more coronary heart disease or disorder or risk associated withlipoprotein gene, such as:

-   -   Apolipoprotein A-I at chromosome location 11q;    -   Apolipoprotein A-IV at chromosome location 11q;    -   Apolipoprotein C-III at chromosome location 11q;    -   Apolipoprotein B at chromosome location 2p;    -   Apolipoprotein C-I at chromosome location 19q;    -   Apolipoprotein C-H at chromosome location 19q;    -   Apolipoprotein E at chromosome location 19q    -   Apolipoprotein A-II at chromosome location 1p;    -   LDL receptor at chromosome location 19p;    -   Lipoprotein(a) at chromosome location 6q;    -   Lipoprotein lipase at chromosome location 8p;    -   Hepatic triglyceride lipase at chromosome location 15q;    -   LCAT at chromosome location 16q; or    -   Cholesterol ester transfer protein at chromosome location 16q.

Optionally, pharmaco-genomic mutation or bioinformatic value isindicated, determined, or generated, in part, to describe or suggest oneor more inborn errors of metabolism disease, disorder, or riskassociated with enzyme, such as:

Disorders of Amino Acid/Organic Acid Metabolism:

-   -   Maple syrup urine disease, associated with or corresponding to        enzyme branched-chain ketoacid decarboxylase;    -   Methylmalonic academia, associated with or corresponding to        enzyme methylmalonic CoA mutase;    -   Multiple carboxylase deficiency, associated with or        corresponding to enzyme biotin responsive carboxylase;        Disorders of Carbohydrate Metabolism:    -   Glycogen storage disease, type 2, associated with or        corresponding to enzyme α-Glucosidase;    -   Galactosemia, associated with or corresponding to enzyme        galactose-1-uridyl transferase;        Disorders of Lysosomal Enzymes:    -   Gangliosidosis (all types), associated with or corresponding to        enzyme β-Galactosidase;    -   Mucopolysaccharidosis (all types), associated with or        corresponding to disease-specific enzyme;    -   Tay-Sachs disease, associated with or corresponding to enzyme        hexosaminidase A;        Disorder of Purine and Pyrimidine Metabolism:    -   Lesch-Nyhan syndrome, associated with or corresponding to enzyme        hypoxanthine-guanine phosphoribosyl transferase; or        Disorder of Peroxisomal Metabolism:    -   Zellweger syndrome, associated with or corresponding to enzyme        long-chain fatty acids.

In clinical, managed-care, hospital, diagnostic, therapeutic, orbiomedical application or embodiment, electronic label processor 40,using one or more firmware, source or object code software, configurablelogic chip or device, digital signal processor, systolic processingarray, or other finite state machine, actually or effectively comparesset of bioinformatic values, preferably associated with same ordifferent temporal states, to determine or otherwise recognize one ormore pharmaco-genomic mutation associated with or corresponding totarget patient, animal, plant, or other biological host.

Furthermore, label apparatus 40 may operate autonomously, in cooperationwith other computer system nodes, clients, or processing elements, tocollect, process and display various host or patient bioinformatic andnon-bioinformatic information. For example, patient information andother personal or medical record data may be received via questionnaireor otherwise retrieved, such as host identification, drug treatment,prescription, and dosage, single or multiple concomitant food or drugallergy, interaction or side effect, pregnancy, lactation, as well asbioinformatic, genetic, proteomic, metabolomic, and other monitored orsensed mutation-related data as described herein.

Label apparatus 40 may be used in time-critical emergency, urgent, ortrauma situation to improve patient health-care diagnosis and treatment,for example, by early-detection, expediting and assisting physician,paramedical, nursing, or other professional analysis and treatment.Sensed or measured bioinformatic value as electronically labeled forindicating pharmaco-genomic mutation information, as described herein,significantly improves quality and accuracy of medication delivery andadministration to identified subgroups of patients having certainadverse response to medication, food, or other treatment.

Additionally, such data may include pharmaco-genomic or pharmaco-kineticclinical or indications based on genetic, proteomic, metabolomic (i.e.,analysis of small organic cell molecules and metabolic responsethereof), or other bioinformatic variant or mutation, or othergenetic-based condition or profile (e.g., sex, race/ethnicity, etc.)such as drugs to be avoided, or considered as alternative. Thusoptimally, host susceptibility or predisposition to toxicity or otheradverse host reaction or side effects to certain identified food, drugs,or other medical treatment may be minimized, mitigated, or eliminatedusing automated rule-based advise or expert system.

For example, label apparatus 40 may alert medical professionals whenhost patient is determined via sense approach to detect pharmaco-genomicmutation described herein that patient ability to produce thiopurineS-methyltransferase (TPMT) enzyme activity is compromised. Here, TPMTgenetic test (commercially available from DNA Sciences (Raleigh, N.C.)enables identification of patient at risk for6-MP/azathioprine/thioguanine toxicity, and improves confidence throughtailored dosing regimens, while minimizing concern over drug-inducedcomplication.

Alternatively, pharmaco-genomic mutation to G protein-coupled receptors(GPCR) molecular target and variant alleles may be detected toelectronically label and thereby effectively modify host drug therapy.Another pharmaco-genomic mutation that may be detected and labeled isenzyme debrisoquine hydroxylase (CYP2D6), isozyme of microsomalcytochrome P450 monooxygenase system; encoding gene is located in CYP2Dgene cluster in contiguous 45-kb region of chromosome 22. Here, at leastnine polymorphisms of CYP2D6 affect metabolism of more than 30 differentpharmaceuticals, including β-adrenergic receptor antagonists,neuroleptics, and tricyclic antidepressants.

Label display 48 visually or audibly indicates to doctor, nurse, orother medical or technical staff textual, symbolic or graphicrepresentation of one or more detected pharmaco-genomic mutation. Suchindication may be network-accessible for modified medical message.

Label apparatus 40 may couple electronically or digitally to hospital,physician, nursing, and other medical staff communication system toenable network-accessible prescription renewal, appointment scheduling,lab-result entry and retrieval, referrals to specialists and diseasemanagement, as well as generally computerized physician orpharmacy-ordering scheme, patient communications, access tobioinformatic test or sensor results, insurance claim status, andbar-coding of pharmaceuticals, and automated medication checks forpossible errors, preferably in accordance with pharmaco-genomic labelingapproach described herein.

Compare method or genetic algorithm may employ simple identical orsubstantial equivalent value check between recently-measured value andpreviously-stored value for same host, for example, after host exposureto radiation or other carcinogenic sources. Such algorithm may beexecuted to adapt iteratively or dynamically in real-time or in multipleor parallel processors based on currently or recently-measured,monitored, or sensed host bioinformatic values, for example using fuzzysystem, Bayesian or neural network, to improve compute or processingperformance by comparing initially values that previously are known orrecorded to be related or likely to be related or otherwise weighted topharmaco-genomic mutation.

Additionally, electronic access to bioinformatic value orpharmaco-genomic mutation information may be restricted, secured,encrypted, or excluded unless the host thereof explicitly or voluntarilyprovides prior informed consent to access such information.

Hence, comparison serves to detect presence or absence of bioinformaticvalue (e.g., oncogene, tumor suppressor gene, allele, enzyme, repeatsequence, micro-deletion, or other mutant gene product, protein, ormetabolome) that causes, or increases or decreases risk of one or morehost disease, disorder, syndrome, allergy, or other biologicalcondition.

Such bioinformatic value or pharmaco-genomic mutation information may bestored in label memory 44 or in other digital storage accessible orotherwise retrievable through network 50. Such stored information may beformatted according to one or more conventional, industry-standard, orotherwise publicly or commercially-available software, processing,storage, and communications protocol, as well as databases formetabolic, signaling, regulatory and pathway data.

Additionally, as appropriate, other genomic relational orobject-oriented knowledge base or data sources may be network-accessed,such as GENBANK, UNIGENE, LOCUSLINK, HOMOLOGENE, ENSEMBLE, GOLDENPATH,or NCICB Cancer Genome Anatomy Project (CGAP). Such information may beaccessed using ontology-based interfaces that are defined to belogically related, for example, using annotation format such asDistributed Annotation System (DAS).

Optionally, bioinformatic value-related function or clinical step may bespecified and otherwise annotated, such as hypothesis definition,experiment design, sample preparation and distribution, experiment run,data acquisition, result analysis, data mining, design refinement,modeling, knowledge discovery, or project report. Additionally, suchfunctions may be applied to bioinformatic data processed by software orhardware analysis tools for pharmacogenomics, gene expression,high-throughput sequencing, or proteomics (functional or structural)use-case domains.

Preferably such stored information complies, at least in part, with dataexchange and management framework and specifications provided byInteroperable Informatics Infrastructure Consortium (I3C), whichtechnical and use-case model documents, and recommended implementations,as described on-line are hereby incorporated by reference as appropriateherein.

For example, one or more I3C-compliant or recommended data format may beemployed during operation of electronic label processor, as describedherein. Accordingly bioinformatic values may be accessed, and displayedor otherwise imaged using electronic display I/O 48 hardware orsoftware, for gel chromatography images, original data from biologicalarrays, arrays of time-series data from mass spectrometry, illustrativefunctional depiction of proteins, simple microscope images, patientrecords with medical images, derived data from multiple or time-seriesimages, electrocardiograms, or original drawings and annotations tomedical images made by examining professionals. On-screen searchcapability enables medical professional quickly to locate and interpretparticular host bioinformatic data, such as gene sequence, protein,enzyme, allele, or other related detail.

Additionally, I3C-compliant or recommended data format may be employedto provide clinical trial FDA pharmacogenomic submission data, includinggenotype, haplotype, phenotype, or derived analysis format; and pathwaysand system biology information for data, models and simulations, forexample of networks and pathways based on pair-wise labeledrelationships between proteins, genes, and RNA transcripts, as well asvirtual cell systems. For example, design synthesis, test, andsimulation of virtual cell system biology enables perturbation ormutagenesis stimulation to predict behavior according to host drugmetabolism, transport, distribution, or excretion.

Network 50 access to various databases or other digital repository maycouple in n-tiered architecture multiple client interfaces, servecomponents, back-end objects and data sources. For example, Netscape orMicrosoft Internet Explorer browsers or applications, e.g., based onJAVA, non-JAVA, PERL, C, C++, or other programming or developmentsoftware, run on client nodes 60 may receive information, such as invarious markup-language, e.g., HTML, XML, etc., from back-end objectsover conventional network messaging or transport protocol, e.g., hypertext transfer protocol (HTTP), TCP Internet Protocol, simple objectaccess protocol (SOAP), file transfer protocol (FTP), HOP, etc.Additionally, Universal Description Discovery Integration (UDDI)registry and Resource Description Framework (RDF) agent advertisingformats may be used.

As described herein, pharmaco-genomic mutation data may be generated anddisplayed by label apparatus 40. Genomic, proteomic, or metabolomicsequence analysis software tool, for example, (e.g., BLAST, TIMELOGIC)may be used by controller 42 to discover or characterize host genomic,proteomic, or metabolomic sequence, acquired and qualified from one ormore sources, such as sensor 49 or database 44. Thus, internal andexternal sequence and protein libraries may be updated and maintained,certain redundant, unqualified or external data being filtered forinternal sequence processing. One or more target, putative or otherwisemutant gene or bioinformatic value is then determined and catalogedeffectively by label apparatus 40.

Optionally, hypothetical function of such determined gene or value maythen be generated manually, automatically, or homologously by findingsimilarity to known or other prior values. Genetic, proteomic, ormetabolomic analysis protocols and similarity analysis may be definedand selected, thereby enabling or constructing functional hypotheses tobe generated, prioritized, or reviewed using sensor measurements orother host evidence.

Proteolysis sample preparation may be performed (e.g., HPLC, gelelectrophoresis), then mass spectroscopy or tandem MS analysis andcompression, quantitization, and fragment size genome analysis forcandidate prediction, proteome or metabolome comparison, and otherquantitative analysis using modeling tools and databases.

The foregoing descriptions of specific embodiments of the invention havebeen presented for purposes of illustration and description. They arenot intended to be exhaustive or to limit the invention to the preciseforms disclosed. Obviously, many modifications and variations arepossible in light of the above teaching, including pharmaco-genomicmutation labeling to alert potential or actual medical associated riskwith organ transplant, paternity identification, genetically-modifiedagricultural crops, antisense and gene vaccine or therapy. Theembodiments were chosen and described in order to explain the principlesand the application of the invention, thereby enabling others skilled inthe art to utilize the invention in its various embodiments andmodifications according to the particular purpose contemplated. Thescope of the invention is intended to be defined by the claims appendedhereto and their equivalents.

What is claimed is:
 1. Apparatus for biological sensing and alerting of TPMT, GPCR, or CYP2D6 pharmaco-genomic mutations device integrated with semiconductor nanocrystal or quantum-dot device for multi-sensing of TPMT, GPCR, or CYP2D6 pharmacogenomic mutations in real-time of the same patient or host to alert potential or actual medical associated risk with organ transplant, paternity identification, genetically-modified agricultural crops, antisense, and gene vaccine or therapy comprising: at least one or more integrated or implantable sensors for real-time detection of TPMT, GPCR, or CYP2D6 pharmaco-genomic mutations of in vivo or in vitro biological material of a patient or host in order to generate a bioinformatic-value signal, wherein said one or more sensor detects the TPMT, GPCR, or CYP2D6 pharmaco-genomic mutations using said semiconductor nanocrystal or said quantum-dot device to sense as detectable label or probe by linking or bonding to one or more affinity molecules of a detectable substance in an analyte in real-time for the same patient or host whereupon nanocrystal probe in response to a first energy associated with a presence of detectable substance within material bonded to the probe excites the nanocrystal in the probe and causes the probe to provide a second energy or generate or fluoresce a distinct wavelength signal indicating the presence, bioinformatic-value signal being formatted according to clinical trial FDA pharmaco-genomic submission data according to the sensing of the TPMT, GPCR, or CYP2D6 pharmaco-genomic mutations consisting essentially of genotype, haplotype, phenotype, or derived analysis format; and pathways and system biology information for data, models, and simulations of networks and pathways, based on pair-wise labeled relationships between proteins, genes, RNA transcripts, and virtual cell systems, whereby design synthesis, test, and simulation of virtual cell system biology enable perturbation or mutagenesis stimulation to predict behavior according to host drug metabolism, transport, distribution, or excretion to alert potential or actual medical associated risk with organ transplant, paternity identification, genetically-modified agricultural crops, anti-sense, and gene vaccine or therapy; software and hardware analysis tool coupled to said at least one integrated or implantable sensor integrated with said semiconductor nanocrystal or said quantum-dot device for multi-sensing of TPMT, GPCR, or CYP2D6 pharmaco-genomic mutations in real-time of the same patient or host, for processing the bioinformatic-value signal to determine pharmaco-genomic mutations associated with said patient or host by comparing electronically the bioinformatic-value signal to determine, via integrated or implantable multi-sensor detection in real-time of the same patient or host, pharmaco-genomic mutations comprising TPMT, GPCR, or CYP2D6, wherein the analysis tool electronically compares the bioinformatic-value signal using simple identical or substantial equivalent value check between recently-measured value and previously-stored value for same host after host exposure to radiation and other carcinogenic sources, whereby such comparison adapts iteratively and dynamically in real-time using multiple and parallel processors based on currently and recently-measured, monitored, and sensed host bioinformatic values using fuzzy system, Bayesian, or neural network to improve compute and processing performance by comparing initially values that previously are known and recorded to be related, and likely to be related or otherwise weighted, to pharmaco-genomic mutation, such that the comparison serves to detect presence or absence of the bioinformatic-value signal consisting essentially of oncogene, tumor suppressor gene, allele, enzyme, repeat sequence, micro-deletion, and other mutant gene product, protein, and metabolome that causes, or increases or decreases risk of one or more host disease, disorder, syndrome, and allergy, thereby enabling the analysis tool to alert potential or actual medical associated risk with organ transplant, paternity identification, genetically-modified agricultural crops, antisense and gene vaccine or therapy, whereby electronic access by the analysis tool to the further modified bioinformatic-value signal is restricted, secured, encrypted, and excluded unless the host explicitly and voluntarily provides prior informed consent to access such information; an alert device coupled to the analysis tool for indicating electronically the determined pharmaco-genomic mutations, wherein said alert device generates visible or audible alert to medical professionals in prioritized or hierarchical manner, to reveal graphically or audibly through I/O in emphasized or highlighted context, higher-risk likelihood or more serious toxicity or patient risk, said alert device further indicates or warns when wrong or inappropriate medication was or is delivered to particular patient having pharmaco-genomic profile, wherein the analysis tool causes the bioinformatic-value signal to annotate clinical hypothesis definition, experiment design, sample preparation and distribution, experiment run, data acquisition, result analysis, data mining, design refinement, modeling, knowledge discovery, or project report according to pharmaco-genomics, gene expression, high-throughput sequencing, or structural or functional proteomics use-case domains, thereby enabling electronic alert of potential or actual medical associated risk with organ transplant, paternity identification, genetically-modified agricultural crops, antisense, and gene vaccine or therapy via integrated or implantable multi-sensor detection in real-time of the same patient or host using integrated semiconductor nanocrystal or quantum-dot device for integrated or implantable multi-sensing of TPMT, GPCR, or CYP2D6 pharmaco-genomic mutations in real-time of the same patient or host; and a display wherein said display is integrated with said analysis tool and said at least one or more integrated or implantable sensors, wherein the display may visually, audibly, or graphically indicate to a physician, nurse, or other medical or technical staff textual, symbolic, or graphical representation of one or more detected pharmaco-genomic mutation or other incorporated I/O at any indicative time from analysis tool such that displayed indication may be network-accessible and said display further comprises an on-screen searching capability for use by a physician, nurse, or other medical or technical staff for potential modification of I/O medical related message representation at any time in-line with real-time said integrated or implantable sensor signal generation.
 2. The apparatus of claim 1 wherein: at least one of the integrated or implantable sensor further comprises a nucleic acid probe for nucleic acid-based diagnostic, de novo sequencing, or detecting reaction between target molecule and probe.
 3. The apparatus of claim 1 wherein: said analysis tool further comprises a TPMT, GPCR, and CYP2D6 test for alerting a medical professional when a patient is at risk for a pharmaco-genomic toxicity.
 4. The apparatus of claim 1 wherein: said alert device indicates a hierarchy or priority via said display associated with the determined pharmaco-genomic mutations associated with a medical or toxic risk after the patient or host is exposed to a radiation or carcinogenic source. 